rs4618985

Positions:

• chr1-12611319-A-C
• chr1-12611319-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004753.7(DHRS3):​c.195+5835T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,148 control chromosomes in the GnomAD database, including 5,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5629 hom., cov: 33)
• Consequence: DHRS3 NM_004753.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968

Genes affected

DHRS3 (HGNC:17693): (dehydrogenase/reductase 3) Predicted to enable NAD-retinol dehydrogenase activity. Predicted to be involved in regulation of retinoic acid receptor signaling pathway and retinoid metabolic process. Predicted to act upstream of or within several processes, including animal organ morphogenesis; negative regulation of retinoic acid receptor signaling pathway; and regulation of ossification. Predicted to be located in endoplasmic reticulum membrane and photoreceptor outer segment membrane. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHRS3	NM_004753.7	c.195+5835T>G		intron_variant		ENST00000616661.5
DHRS3	XM_047434406.1	c.-10944T>G		5_prime_UTR_variant	1/6
DHRS3	NM_001319225.2	c.-61+5241T>G		intron_variant
DHRS3	XM_006711036.3	c.195+5835T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHRS3	ENST00000616661.5	c.195+5835T>G		intron_variant		1	NM_004753.7	P1
DHRS3	ENST00000464917.5	c.-61+5241T>G		intron_variant		3
DHRS3	ENST00000482265.1	n.137+5241T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40854 AN: 152028 Hom.: 5620 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40880 AN: 152148 Hom.: 5629 Cov.: 33 AF XY: 0.267 AC XY: 19854 AN XY: 74380

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.284

Alfa AF: 0.270 Hom.: 3562

Bravo AF: 0.268

Asia WGS AF: 0.299 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4618985; hg19: chr1-12671324;